Although cholinergic agents are potent stimulants of pancreatic secretion, little is known about the distribution of muscarinic receptors within the pancreatic acinar cell versus those which are found on the cell surface. Furthermore, very little is currently known about the rates of turnover of these or any other pancreatic acinar cell receptors. In this investigation the muscarinic binding sites in rat pancreatic acinar cells will be blocked with PrBCM, a long acting muscarinic blocking agent. The rate of onset of pharmacologic activity and time course of recovery of PrBCM inactivation of muscarinic receptors will be studied and compared to its effects on the blockade of specific 3H-methyl scopolamine binding sites in intact cells and subcellular fractions. The rate of reappea;rance of specific methyl scopolamine binding sites will be used as a measure of receptor turnover. The possible effects of PrBCM and desensitizing doses of cholinergic agonists and metabolic inhibitors on receptor turnover and high and low affinity agonist binding sites will be studied. Since more information about the fundamental mechanism involved in pancreatic secretion is required for an understanding of the secretory defects which occur during cystic fibrosis, this study should contribute to an understanding of the pathophysiology of pancreatic disease and other pancreatic diseases. Studies will be performed on human pancreatic tissue as it becomes available from patients who require pancreatic surgical procedures.